Chapter 21: Carboxylic Acid Derivatives

Start with: Use: Product: Notes

carboxylic amides and nitriles require

Hydrolysis H+ or -OH carboxylic acid
derivative stronger conditions (heat)
R''-OH (excess)/
Transesterification ester different ester
H+ or -OR''
acid/acid
LiAlH4 1o alcohol aldehyde intermediate
chloride/ester
Reduction Li(t-BuO)3AlH
acid chloride aldehyde
/ether
amide 1) LiAlH4 2) H2O amine
ester/acid 1) 2 R''-MgX
Grignard Addition 3o alcohol alkoxide salt intermediate
chloride 2) H3O+
H2O carboxylic acid

R-'OH ester

R'-NH2 amide

R'-COOH anhydride

1) LiAlH4 2) H2O 1o alcohol

Reactions of Acid
acid chloride
Chlorides
1) 2 R'MgX 2) H2O 3o alcohol

R2CuLi ketone
Reactions of Acid
acid chloride
Chlorides

Chapter 21: Carboxylic Acid Derivatives

Li(t-BuO)3AlH
aldehyde
/ether

activated benzene acylbenzene

Synthesis of
carboxylic acid acid chloride acid anhydride
Anhydrides
H2O carboxylic acid
Reactions of
anhydride R'OH/H+ ester
Anhydrides
R'NH2 amide

carboxylic
acid/acid
R'OH/H+ ester
Synthesis of Esters chloride/anhydrid
e/ester

carboxylic acid CH2N2 methyl ester

carboxylic acid +
H2O/H+ or -OH
alcohol
different ester +
R''OH/H+ or -OR'' transesterification
alcohol

Reactions of Esters ester R''NH2 amide + alcohol

1) LiAlH4 2) H2O 1o alcohol +

alcohol
Reactions of Esters ester

Chapter 21: Carboxylic Acid Derivatives

1) 2 R''MgX 3o alcohol +
2) H2O alcohol
distilling out the water formed
Lactone Formation hydroxy acid H+ lactone drives the reaction past
equilibrium

carboxylic acid R'NH2 (300o C) amide

acid chloride 2 R'2NH amide

Synthesis of Amides
amide +
anhydride R'2NH
carboxylic acid
ester R'NH2 amide + alcohol

nitrile H2O/H+ or -OH 1o amide

H2O/H+ or -OH carboxylic acid

amide
1) LiAlH4 2) H2O amine
Reactions of Amides
Br2, -OH 1o amine Hoffmann Rearangement
o
1 amide
POCl3 nitrile
Formation of
amino acid heat lactam
Lactams

1o amide POCl3 nitrile

Synthesis of Nitriles
 Chapter 21: Carboxylic Acid Derivatives

alkyl halide NaCN nitrile

Synthesis of Nitriles diazonium salt
CuCN aryl nitrile
(Ar-NN)

ketone/aldehyde HCN/KCN cyanohydrin

amide, then
+ -
H2O/H or OH carboxylic acid
(with heat)
Reactions of Nitriles nitrile
1) LiAlH4 2) H2O amine

1) R'MgX 2) H3O+ ketone imine salt intermediate

Thioester Formation carboxylic acid R'SH thioester